A phase II open-label randomized study to assess the efficacy and safety of selumetinib (AZD6244 [ARRY-142886]) versus capecitabine in patients with advanced or metastatic pancreatic cancer who have failed first-line gemcitabine therapy
Abstract
Selumetinib is a potent, selective MEK inhibitor with efficacy in several tumor models. This study compared selumetinib with capecitabine in patients with advanced or metastatic pancreatic cancer who had been pretreated with a gemcitabine-based regimen. In this randomized, multicenter phase II study (NCT00372944), patients received either 100 mg oral selumetinib twice daily or 1,250 mg/m(2) oral capecitabine twice daily for 2 weeks followed by a 1-week break, given in 3-weekly cycles. The primary endpoint was overall survival. In all 70 patients were randomized. The median survival was 5.4 months in the selumetinib group and 5.0 months in the capecitabine group (hazard ratio 1.03; two-sided 80% confidence interval = 0.68,1.57; P = 0.92). Disease progression events occurred in 84% and 88% of patients in the selumetinib and capecitabine treatment groups, respectively. Gastrointestinal adverse events (nausea, vomiting and diarrhea) were commonly observed in both treatment groups. Other frequently reported adverse events were acneiform dermatitis and peripheral edema with selumetinib, and palmar-plantar erythrodysaesthesia with capecitabine. There was no statistically significant difference in overall survival between selumetinib and capecitabine as second-line treatment in patients with advanced pancreatic cancer. Selumetinib was well tolerated with a manageable safety profile.
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Phase II trials found that CI-1040 and selumetinib, both MEK inhibitors, produced responses no better than chemotherapy.
“Single agent phase II trials of the MEK inhibitors CI-1040 and selumetinib showed that these agents were well tolerated but did not give superior response compared to chemotherapy (87, 88).”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [88]
Phase II testing showed that the MEK inhibitors CI-1040 and selumetinib had acceptable tolerability.
“Single agent phase II trials of the MEK inhibitors CI-1040 and selumetinib showed that these agents were well tolerated but did not give superior response compared to chemotherapy (87, 88).”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [88]
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- Authors
- Bodoky, G., Timcheva, C., Spigel, D. R., La Stella, P. J., Ciuleanu, T. E., Pover, G., & Tebbutt, N. C.
- Affiliations
- Sarah Cannon (US)
- Institute of Oncology Prof. Dr. Ion Chiricuta (RO)
- AstraZeneca (United Kingdom) (GB)
- Venue
- Investigational New Drugs
- Published
- 2011-05-19
- Volume
- 30
- Issue
- 3
- Pages
- 1216-1223
- ISSN
- 0167-6997 (ISSN-L)
- 1573-0646
- OpenAlex
- W2025749621
- Cited by
- 236
- References
- 34
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 16 · 2023: 13 · 2022: 15 · 2021: 14 · 2020: 16 · 2019: 8 · 2018: 15 · 2017: 26 · 2016: 21 · 2015: 34 · 2014: 17 · 2013: 12 · 2012: 12
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Update notices
- erratum (2011-07-26)
- Open access
- closed
- Licence
- Locations
- Investigational New Drugs (publishedVersion)
- PubMed (publishedVersion)
- Funders
- AstraZeneca
- F. Hoffmann-La Roche
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- selumetinib, capecitabine, advanced pancreatic cancer, metastatic pancreatic cancer, MEK inhibitors, second-line therapy, gemcitabine-refractory disease, overall survival, drug safety, adverse events
- MeSH terms
- Capecitabine, Gemcitabine, Adult, Aged, Aged, 80 and over, Antimetabolites, Antineoplastic, Benzimidazoles, Deoxycytidine, Female, Fluorouracil, Humans, Male, Middle Aged, Pancreatic Neoplasms, Treatment Outcome, Drug Resistance, Neoplasm, MAP Kinase Kinase Kinases, Protein Kinase Inhibitors, Young Adult
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